FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis

@article{Chinnaiyan1995FADDAN,
  title={FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis},
  author={Arul M. Chinnaiyan and Karen O'rourke and Muneesh Tewari and Vishva M. Dixit},
  journal={Cell},
  year={1995},
  volume={81},
  pages={505-512}
}
Using the cytoplasmic domain of Fas in the yeast two-hybrid system, we have identified a novel interacting protein, FADD, which binds Fas and Fas-FD5, a mutant of Fas possessing enhanced killing activity, but not the functionally inactive mutants Fas-LPR and Fas-FD8. FADD contains a death domain homologous to the death domains of Fas and TNFR-1. A point mutation in FADD, analogous to the lpr mutation of Fas, abolishes its ability to bind Fas, suggesting a death domain to death domain… 
Phosphorylation of FADD/MORT1 and Fas by kinases that associate with the membrane-proximal cytoplasmic domain of Fas.
TLDR
Findings suggest that, similar to the Fas-related p55 TNFR, the membrane-proximal region of Fas likely participates in signaling.
The Death Domain of FADD Is Essential for Embryogenesis, Lymphocyte Development, and Proliferation*
TLDR
A reverse genetic study has revealed a previously unappreciated role of the FADD death domain, which likely functions as a molecular switch regulating two distinct signals leading to apoptosis and cell proliferation and is critical for embryogenesis, lymphocyte development, and proliferation.
Regulation of Fas-associated Death Domain Interactions by the Death Effector Domain Identified by a Modified Reverse Two-hybrid Screen*
TLDR
Data indicate that in contrast to current models, the death effector domain of FADD is involved in interaction with Fas, and a modified reverse two-hybrid method is developed that can identify mutations, which inhibit some protein-protein interactions without affecting other interactions.
NMR structure and mutagenesis of the FADD (Mort1) death-effector domain
TLDR
A hydrophobic region of the FADD death-effector domain that is not present in the death domains is vital for binding to FLICE and for apoptotic activity.
Structural and biochemical analysis of the death domain complex formed at the Fas receptor
TLDR
It was found that residues from many surface regions of Fas-DD are crucial for the FADD-DD interaction, which has potentially important implications for the nature of the organisation of the death domains in the death inducing signalling complex (DISC) formed at the Fas receptor.
Dissecting Fas signaling with an altered-specificity death-domain mutant: requirement of FADD binding for apoptosis but not Jun N-terminal kinase activation.
TLDR
It is suggested that FADD and Daxx activate two independent pathways downstream of Fas and confirm the essential role of FADD binding in apoptosis induction.
The Solution Structure of FADD Death Domain
TLDR
The interactions between the death domains of Fas and FADD analyzed by site-directed mutagenesis indicate that charged residues in helices α2 and α3 are involved in death domain interactions, and the interacting helices appear to interact in anti-parallel pattern.
Formation of the death domain complex between FADD and RIP1 proteins in vitro.
TLDR
A molecular docking model using homology modeling based on the structures of FADD and RIP1 found that two structure-based mutants of the FADD DD were able to bind to the RIP1 DD, and two mutations were found that structurally destabilized the complex, thus disrupting the interaction.
CASH, a Novel Caspase Homologue with Death Effector Domains*
TLDR
The findings suggest that CASH acts as an attenuator and/or initiator in CD95 and CD120a signaling for cell death, through a shared N-terminal sequence motif, the death effector domain.
RICK, a Novel Protein Kinase Containing a Caspase Recruitment Domain, Interacts with CLARP and Regulates CD95-mediated Apoptosis*
TLDR
RICK represents a novel kinase that may regulate apoptosis induced by the CD95/Fas receptor pathway, and both the kinase domain and caspase-recruitment domain were required for RICK to promote apoptosis.
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